U.S. Pat. No. 4,727,109 relates to a pharmaceutical preparation having an active substance of low solubility in water and gastric juices. The active substance is dissolved in a carrier system that consists of a hydrophobic component such as vegetal oils, a hydrophilic component such as polyethylene glycol and a solubilizer such as triethylcitrate. The pharmaceutical preparation is contained in a hard gelatin capsule.
EP 0127297 relates to a vitamin or mineral composition comprising a vitamin or a mineral and at least a polyoxyethylene sorbitan ester. Optionally the composition may contain a non-toxic alcohol or other diluents such as vegetal oils and derivatives. The composition is contained in a solid unit dosage form such as a hard shell capsule or a soft elastic capsule. The capsule is preferably made of gelatin.
U.S. Pat. No. 6,056,971 relates to a method for enhancing the dissolution and bioavailability properties of a dietary supplement that can be e.g. Coenzyme Q 10 (ubiquinone). The Coenzyme Q 10 is contained in a unit dosage form a gelatin capsule.
Capsules are widely used in the pharmaceutical industry as well as in the health food supplement market. The main usage thereof is as a dosage form for solid, semi-solid, liquid, pellet or herbal preparations. A primary objective of these dosage forms is to have a good disintegration after being administrated in order to enable a fast dissolution of the active substances in the appropriate digestive organ. Any delay of the disintegration would consequently retard or even reduce the effect of the drug. Consequently, this disintegration characteristic has to remain unchanged over time when finished products are stored prior to use.
The traditional material for forming the capsule shell is gelatin, because it has correct and quite ideal properties. Conventional hard capsules are made with gelatin by dip moulding processes. For the industrial manufacture of pharmaceutical capsules gelatin is most preferred for its gelling, film forming and surface active properties. Traditionally, gelatin is produced by extraction from collagen containing mammalian tissues, particularly such as pig skin and bovine bone.
Gelatin has some disadvantages, however, which make it necessary to have other capsule shell materials available. A major unfavourable aspect is the animal origin of gelatin. Other disadvantages are the inconveniences of relatively high water content (10-17%) and the loss of elasticity with decreasing water content. Furthermore gelatin capsules are sensitive to heat and humidity which affect the usability of the product. In particular soft gelatin capsules are known to aggregate under hot and humid conditions. Under dry conditions gelatin films may induce static charge build up affecting later processing.
It has long been recognized that gelatin capsules become brittle when they lose some of their moisture content. Water acts as a plasticizer in gelatin films and when the level falls below about 10%, they become very brittle. On the other hand when the water content increases the capsule shell can weaken and finally leakage will occur.
The formulation of drugs into soft gelatin capsules has gained popularity throughout the past decade due to the many advantages of this dosage form. The bioavailability of hydrophobic drugs can be significantly increased when formulated into soft gelatin capsules. Many problems associated with tableting, including poor compaction and lack of content or weight uniformity, can be eliminated when a drug is incorporated into this dosage form.
Soft gelatin capsules generally contain the medicament dissolved or dispersed in oils or hydrophilic liquids (i.e. fill liquid). The inherent flexibility of the soft gelatin capsule is due to the presence of plasticizers and residual moisture in the capsule shell. A disadvantage of soft gelatin capsules is that the atmospheric moisture may permeate into the capsule shell or into the fill. Volatile components in soft gelatin capsules may escape into the atmosphere. These liquid mixtures are very often dispersions which show a reduced bioavailability in particular in the gastrointestinal tract. In order to overcome these problems it has been suggested to use more complex solvent systems in gelatin capsules.
Other disadvantages are the problems related to capsule shell/contents interactions or unacceptable taste and smell.
Therefore, there is a need to provide containers in line with customer dietary (e.g. vegetarian) and religious orientations and at the same time to enhance bioavailability of low soluble substances by providing an appropriate solvent that, among its high solubilising capability, is also compatible with non-animal based containers and low soluble substances.
The object of the present invention is, therefore, the provision of an improved delivery system comprising a container and a liquid fill which overcomes the above mentioned draw backs of the prior art compositions.
This object is solved according to a delivery system, a process for preparation thereof and uses according to the independent claims.
Further advantageous features, aspects and details of the invention are evident from the dependent claims, and the description. The claims are to be understood as a first non-limiting approach to define the invention in general terms.